Disitamab Vedotin Combined With Tislelizumab for Her2 Overexpressing High-Risk Non-Muscle-Invasive Urothelial Bladder Carcinoma Which is Not Completely Resectable

An Open Label, Phase 2 Study of Disitamab Vedotin Combined With Tislelizumab for Patients With Her2 Overexpressing (IHC2+ or 3+) High-Risk Non-Muscle-Invasive Urothelial Bladder Carcinoma Which is Not Completely Resectable

This is a phase II study to determine the safety and efficacy of Disitamab Vedotin when given in combination with Tislelizumab as treatment for patients with Her2 overexpressing high-risk non-muscle-invasive bladder cancer (HR NMIBC) which is not completely resectable. Patients will receive treatment with Disitamab Vedotin in combination with tislelizumab every 3 weeks for 4 treatment cycles over 12 weeks followed by transurethral resection biopsy.

Study Overview

• Status: Recruiting
• Conditions: Her2 Overexpressing High-Risk Non-Muscle Invasive Bladder Urothelial Carcinoma
• Intervention / Treatment: Drug: Disitamab Vedotin Tislelizumab; Drug: Disitamab Vedotin

• Study Type: Interventional
• Enrollment (Anticipated): 176
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300211
      • Recruiting
      • Tianjin Medical University Second Hospital
      • Principal Investigator: Hailong Hu, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years;
2. Urothelial carcinoma with Her2 IHC 2+ or 3+;

3. High-risk non-muscle-invasive urothelial carcinoma or high-risk non-muscle-invasive urothelial carcinoma as the main pathological component > 50%, difined as following:

   a. T1 b. High-grade Ta c.Carcinoma in situ(CIS);

4. Multi-point biopsy of bladder shows there are more than 2 section and over 3 points of pathological specimens are diagnosed as above, meanwhile, the tumor has to be diagnosed as not completely resectable by at least 2 senior urologist;
5. Agreed to provide tissue examination samples (for detection of PD-L1 expression, tumor mutation load, IHC, detection of DNA and RNA, etc;)

6. Organ function level must meet or under the support treatment meet the following requirements:

   • Hematological indexes: neutrophil count >= 1.5x10^9/L, platelet count >= 100x10^9/L, hemoglobin >= 9.0 g/dl;
   • Liver function: total bilirubin <=1.5 ULN, alanine aminotransferase and aspartate aminotransferase <=2.5 ULN（patient with metastatic liver cancer：aminotransferase <=5.0 ULN）;
   • Renal function: creatinine ≤ 1.5 times the upper limit of normal, and creatinine clearance ≥ 50 ml/min;
7. The subjects volunteered to join the study, signed informed consent, and had good compliance with follow-up;

Exclusion Criteria:

1. Active, known or suspected autoimmune diseases;
2. History of primary immunodeficiency;
3. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
4. Pregnant or lactating female patients;
5. Untreated acute or chronic active hepatitis B or hepatitis C infection. Under the condition of monitoring the virus copy number of patients receiving antiviral treatment, doctors can judge whether they are in line with the patients' individual conditions;
6. Prior use of immunosuppressive drugs within 4 weeks prior to the start of treatment, excluding nasal and inhaled corticosteroids or physiological doses of systemic steroids (i.e. not more than 10 mg / day prednisolone or other corticosteroids with the same physiological dose);
7. Known or suspected allergy to disitamab vedotin or tislelizumab;
8. Have a clear history of active tuberculosis;
9. Participating in other clinical researchers;
10. Men with reproductive capacity or women who are likely to become pregnant do not take reliable contraceptive measures;

11. Uncontrolled concurrent diseases, including but not limited to:

    • HIV infected (HIV antibody positive);
    • Severe infection in active stage or poorly controlled;
    • Evidence of serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension [i.e. hypertension greater than or equal to CTCAE grade 2 after drug treatment]);
    • Patients with active bleeding or new thrombotic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Disitamab Vedotin and Tislelizumab; Disitamab Vedotin 120mg IV on day 1 in combination with Tislelizumab 200mg IV on day 2 every 3 weeks for 3 or 4 cycles followed by transurethral resection biopsy.	Drug: Disitamab Vedotin Tislelizumab; Disitamab Vedotin 120mg will be administered on Day 1 of each cycle for 4 treatment cycles;Tislelizumab 200mg will be administered on Day 2 of each cycle for 4 treatment cycles.; Other Names: KEYNOTE-057
OTHER: Disitamab Vedotin; Disitamab Vedotin 120mg IV on day 1 every 3 weeks for 3 or 4 cycles followed by transurethral resection biopsy.	Drug: Disitamab Vedotin; Disitamab Vedotin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete Response (CR) Rate	At the time of transurethral resection biopsy (within 9 or 12 weeks of the first dose of disitamab vedotin)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cystectomy-Free Survival (CFS)	defined from D1 of treatment until cystectomy	up to 3 years
Duration of Response (DOR)		up to 3 years
Progress Free Survival（PFS）		up to 3 years
Recurrence Free Survival（RFS）		up to 3 years
Event-Free Survival（EFS）	defined from D1 of treatment until the time of any events，included progressive disease，discontinue treatment for any cause or death	up to 3 years
Number of adverse events and severity by grade (CTCAE)	Safety and toxicity will be characterized according to the reported adverse event (AE) profile using NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0, as well as a patient questionnaire derived from the Patient Reported Outcomes (PRO)-CTCAE and Patient Reported Outcomes Measurement Information System (PROMIS).	12 weeks of treatment plus 30 days for toxicity followup
Her2 status		up to 3 years
PD-1 expression status		up to 3 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University Second Hospital
• Investigators: Principal Investigator: Hailong Hu, Tianjin Medical University Second Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 23, 2021
• Primary Completion (ANTICIPATED): February 1, 2025
• Study Completion (ANTICIPATED): July 1, 2025

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (ACTUAL): August 10, 2022

Study Record Updates

• Last Update Posted (ACTUAL): August 10, 2022
• Last Update Submitted That Met QC Criteria: August 9, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Tislelizumab; Disitamab Vedotin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Carcinoma; Urinary Bladder Neoplasms
• Other Study ID Numbers: TRUCE-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No